This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. FTMS is the instrument of choice for the analysis of biological molecules due to its high mass accuracy, resolving power, and wide dynamic range. There is a potential for improving these performance parameters further, if an FTMS is enabled to detect a single ion with a unit charge. Thus, recently there has been a push in the FTMS community to improve the detection sensitivity of an FTMS1. Unit charge detection sensitivity can be achieved by improving the signal to noise ratio of the detection circuit in an FTMS. Noise in an FTMS preamplifier circuit can be minimized by building a differential design using low noise active devices. The signal to noise ratio of this preamplifier circuit can be enhanced further by cooling the circuit to low temperatures to reduce the thermal (Johnson) noise2. Initial prototypes of such a low noise wideband amplifier were built using silicon based components. A classical op-amp based instrumentation amplifier, and a JFET-based three-stage amplifier were designed and characterized for their performance. The results demonstrated that both of them provide sufficient gain. Further, the three-stage amplifier has a superior noise performance. In addition, a comparative study between the three-stage amplifier and a commercial amplifier on FTMS indicated that the former provides a signal to noise ratio about 2.5 times higher than that of the commercial amplifier. However, none of these amplifiers could meet the bandwidth requirement of 10 MHz. These preliminary amplifiers were built using silicon based components. Thus, they cannot work at cryogenic temperatures, since carrier freeze-out generally occurs in silicon below 20 Kelvin. However, GaAs is a compound semiconductor material which has higher electron mobility compared to silicon and can be operated at cryogenic temperatures (~4K). Here we report ongoing progress in the development of a cryogenic low noise preamplifier based on these devices for FTMS. A simple inverting amplifier which represents half of the ultimate differential cryo-amplifier was designed using commercial GaAs HEMTs as shown in Fig. 1. The GaAs HEMTs used have a Noise Figure of 1.2 dB at 12 GHz3. The gain of the amplifier is equal to the product of the transconductance (gm) and the drain resistance (RD). The HEMT was operated at VDS = 2 volts and IDS = 5mA. The measured transconductance of the device at the above bias point was approximately 30 mS. The expected voltage gain was around 6 (gm X RDS). A plot of the measured gain versus frequency is shown in Fig. 2. Further analysis of the inverting preamplifier revealed that the operating point of the amplifier was unstable. Further tests using high frequency spectrum analyzer showed that the amplifier was oscillating at a frequency of 6.2 GHz, without input signal. The fully-differential preamplifier is being designed to be mounted on the detection plates of the cell, but the intrinsic cell capacitance, ~ 12 pF per plate, limits the design. This capacitance, in parallel with the input impedance of the amplifier defines the high frequency response of the amplifier. Even so, the current preamplifier design yielded a gain of 5 and a 3 dB bandwidth of 1.6 MHz, using a 1 Mohm input resistor at room temperature. This design should allow a five-fold improvement in signal to noise ratio compared to current designs, and has been designed using components that are compatible with cryogenic temperature operation, which will potentially reduce the noise another ~8 fold. It is expected that the bias point of the transistors will change with temperature, thus requiring adjustment of the input bias potential at low temperatures. To test this, a simple cryostat was constructed for optimizing this amplifier at low temperatures. The system has now been tested on the actual mass spectrometer and it works well at low temperatures. Furthermore, the pramplifier has been shown to have 25 fold lower noise than the original IonSpec, in-vacuum preamplifier on the 7T MALDI-FTMS, which can be improved a further 5 fold by using batteries rather than switching power supplies for Vdd and Vss. A version of this preamplifier which uses GaAs MESFET transistors suitable for operation at 4K is now constructed and tested both at 4K and at 14T and is currently being installed in the Cryogenic FTMS. The first room-temperature version of this amplifier was published in JASMS. The cryogenic version of this amplifier was completed and tested, and an article has recently been published in IEEE Transactions on Applied Superconductivity 2008, 18, 1781-1789. Raman Mathur completed his Ph.D. on this project, so most likely there will not be more progress on this project for some time.